[The role of oxidative stress in hemorrhagic stroke and restorative effects of Mexidol]. / Rol' oksidativnogo stressa pri ostrom eksperimental'nom gemorragicheskom insul'te i terapevticheskie effekty Meksidola.

OBJECTIVE: Identification of the role of oxidative stress in the development of disorders that occur in hemorrhagic stroke (HS, post-traumatic intracerebral hematoma), and the study of the effects of Mexidol on neurological and cognitive deficits in HS with an analysis of the relationship between the therapeutic effects of the drug in HS with its antioxidant effect. MATERIAL AND METHODS: The study was carried out on mature outbred male rats weighing 260-280 g. HS was created by destruction of the brain tissue in the area of the capsula interna, with the introduction of blood into the site of injury. On the 1st, 7th, and 14th days after HS modeling, death, neurological deficits (McGrow scale, rotating rod), convulsive manifestations, and cognitive impairment were recorded in rats; blood plasma and homogenates of the cerebral cortex of rats. Mexidol was administered after the HS operation: first at a dose of 150 mg/kg, intraperitoneally, for 3 days and then 75 mg/kg, orally (from the 4th to the 14th day). RESULTS: Mexidol in rats with HS significantly increases the survival rate of animals, reduces the manifestations of neurological deficits according to the McGrow scale (playpen movements, paresis of 1-4 limbs, paralysis of the lower limbs, lateral position), eliminates individual motor convulsive manifestations, restores impaired coordination of movements (rotating rod test) and improves, impaired HS, learning and memory processes. Mexidol normalizes the concentration of TBA-active products in the blood of animals and homogenates of the cerebral cortex of rats, both a day and 7 days after HS modeling. CONCLUSION: The data obtained indicate the involvement of oxidative stress as a chain of pathogenesis in the development of disorders in HS and the ability of Mexidol to alleviate neurological deficits, convulsive manifestations and cognitive impairment in HS, which is accompanied by a decrease in oxidative stress. All this justifies the importance of the use of Mexidol in patients with hemorrhagic stroke, posttraumatic intracerebral hematoma and determines the features of its therapeutic effects.

Assessment of Susceptibility of Outbred Albino Rats to the Formation of Depression-Like State of Learned Helplessness.

Learned helplessness (a model of depression-like state) was developed in rats by exposure to repeated inescapable electric stimulation and evaluated by the absence of attempts to escape when it could be performed. In randomly grouped outbred white rats, 37.5% animals after the above procedure meet the criterion of learned helplessness. On experimental day 14, the latent period and the number of applied electric shocks prior to the first escape to the safe compartment in rats with learned helplessness were significantly higher than in the control, but no significant differences in these parameters were observed on day 21. The Porsolt forced swimming test performed on days 14 and 21 revealed no differences from the control group. After the rats were divided into low- and high-active subgroups according to their open field behavior, 35% rats with learned helplessness were in the low-active subgroup group and 30% rats with learned helplessness were in the high-active subgroup. On day 14, the parameters of learned helplessness significantly surpassed the control levels only in the low-active subgroup. Only in rats with learned helplessness and low activity in the open field, the immobility time in the Porsolt test was longer than in control low-active rats. These findings attest to advisability of preliminary splitting of outbred animals by their open-field behavior into low- and high-active subgroups and the use of only animals for modeling learned helplessness.

Behavioral Effects of Dimeric Dipeptide BDNF Mimetic GSB-106 in a Rat Model of Depressive-Like State.

The effects of GSB-106, a low-molecular mimetic of BDNF loop 4, that represents a substituted dimeric dipeptide bis (N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide, on cognitive and motor impairments in a model of a depressive-like state in rats caused by unavoidable electric foot-shock were studied using active avoidance and open-field tests. GSB-106 (0.5 mg/kg, per os, 10 days) completely restored the number of avoidance reactions that was reduced in rats exposed to foot-shock and the percentage of trained rats in active avoidance training. In the open-field test, the peptide restored reduced horizontal activity and the number of explored holes. Thus, GSB-106 corrected impaired learning and memory, as well as locomotor activity and exploratory behavior in a model of depression in rats.

[Neuroprotective and antiamnesic effects of GK-2h dipeptide HNGF mimetic on a model of experimental ischemic stroke of brain cortex prefrontal areas].

Neuroprotective and antiamnesic effects of human nerve growth factor (HNGF) synthetic dipeptide mimetic bis-(N-monosuccinyl-glycyl-lysine)hexamethylenediamide (GK-2h) has been studied on a model of bilateral photochemically induced focal ischemical brain injury in prefrontal cortex of rats. It is established that a single intraperitoneal injection of GK-2h (0.1 mg/kg) 1 h or 4 h after operation, followed by injections on the 2nd, 4th and 8th days after operation, results (on the 9th day) in reduction of the cortical infarction volume by 47 or 65%, and leads to restoration of the passive avoidance reflex (acquired before experimental ischemic insult) by 42 and 60%, respectively. It is concluded that GK-2h possesses significant neuroprotective properties.

[Comparative study of himantane and amantadine effects in experimental intracerebral posttraumatic hematoma].

Effects of the novel antiparkinsonian drug himantane and amantadin were studied in rats with intracerebral posttraumatic hematoma. Drugs were administered first at 3.5 hours after surgery and then for 4 consecutive days. Effects were registered on days 1, 3, 7 and 14 after surgery. It was shown that both drugs significantly decreased mortality and improved motor activity, exploratory behavior and memory. Amantadin was more effective in tests for motor activity and exploratory behavior. Himantane 5 mg/kg i.p demonstrated the more pronounced activity in restoring memory. The results obtained testify for neuroprotective properties of the novel antiparkinsonian drug himantane.